The Stimulatory Effect of IL-1on The Insulin Secretion and Its Relating Factors

Jeong, In Kyung; Oh, Seung Hoon; Kang, Tong Mook; Jeong, Jae Hoon; Min, Yong Ki; Lee, Myung Shik; Lee, Moon Kyu; Kim, Kwang Won

Abstract

BACKGROUND: The inhibitory effect of IL-1 on the insulin secretion has been validated in pathogenesis of type 1 diabetes, but complex results about the stimulatory effect of IL-1 have been reported. The aims of this study are to clarify the effects of IL-1 on insulin secretion of pancreatic islets and to investigate the mechanisms in terms of preproinsulin synthesis, inducible NOS expression, and calcium channel activity.
METHODS
Islets were isolated from male Sprague-Dawley (SD) rat by modified Lacy-Kostianovsky's method. After islets were treated with different concentrations (0, 0.5, 5, 50, 500 pmol/L) and exposure time (2, 6, 24 hours) of IL-1 , morphology, viability, static stimulation of insulin to glucose, insulin content, preproinsulin mRNA expression, iNOS mRNA expression and calcium channel activity were measured.
RESULTS
1) Viability of islets was reduced in high concentrations of long term exposure of IL-1 . 2) Insulin secretion was stimulated in islets treated with 5, 50, and 500 pmol/L of IL-1 for 2 hours and 0.5 pmol/L for 6 hours. It was inhibited in 5, 50, and 500 pmol/L for 6 and 24 hours. 3) Insulin content was not significantly different regardless of concentration and exposure time of IL-1 . 4) Preproinsulin mRNA expression increased in islets treated with 50, 500 pmol/L of IL-1 for 2 hours. After 24 hours, it decreased in dose dependent manner. 5) iNOS mRNA expression was detectable after 2 hours in the presence of IL-1 , peaks at 6 hour and decreased after 24hours. It was increased above 5 pmol/L of IL-1 in dose dependent manner. 6) Activities of the voltage-dependent Ca2+ channels were not different among groups.
CONCLUSION
IL-1 plays a positive role in terms of insulin secretion and insulin synthesis in high concentration of short term or low concentration of long term. These effects of IL-1 might be neither dependent of iNOS pathway nor Ca2+ channel activity.